Decoded: How cancer cells cripple immune system

5 days ago

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New York, Aug 9: Researchers have found that cancer cells send out biological "drones" to fight the immune system and survive.

The study showed that cancer cells release "drones" -- small vesicles called exosomes circulating in the blood and armed with proteins called PD-L1 that cause T-cells to tire before they have a chance to reach the tumour.

The research offers a paradigm-shifting picture of how cancers take a systemic approach to suppressing the immune system.

In addition, it also points to a new way to predict which cancer patients will respond to anti-PD1 therapy that disrupts immune suppression to fight tumours.

"Immunotherapies are life-saving for many patients with metastatic melanoma, but about 70 per cent of these patients don't respond," said Guo Wei, Professor at the University of Pennsylvania.

"These treatments are costly and have toxic side effects so it would be very helpful to know which patients are going to respond," Wei added.

Anti-PD1 therapy blocks interaction between PD-1 -- a protein on the surface of T-cells -- and PD-L1, PD-1's counterpart molecule on tumour cells, thus reinvigorating T-cells and allowing them to unleash killing power on the tumour.

In the study, published in the journal Nature, the team found that exosomes from human melanoma cells also carried PD-L1 on their surface. Exosomal PD-L1 can directly bind to and inhibit T-cell functions.

Identification of the exosomal PD-L1 secreted by tumour cells provides a major update to the immune checkpoint mechanism, and offers novel insight into tumour immune evasion.

According to the researchers, exosomes are tiny lipid-encapsulated vesicles with a diameter less than 1/100 of a red blood cell.

Since a single tumour cell is able to secrete many copies of exosomes, the interaction between the PD-L1 exosomes and T-cells provides a systemic and highly effective means to suppress anti-tumour immunity in the whole body. This may explain why cancer patients might have weakened immune system, they noted.